Unlocking the potential of engineered immune cell therapy for solid tumors

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 29, 2025

Language: Английский

---

Efficacy of TIL Therapy in Advanced Cutaneous Melanoma in the Current Immuno-oncology Era: Updated Systematic Review and Meta-analysis

Annals of Oncology, Journal Year: 2024, Volume and Issue: 35(10), P. 860 - 872

Published: July 23, 2024

Language: Английский

---

Optimizing TIL therapy for uveal melanoma: lessons learned and unlearned from cutaneous melanoma

Immunotherapy, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 9

Published: March 18, 2025

Adoptive transfer of tumor infiltrating lymphocytes (TIL-ACT) is a personalized cancer therapy that harnesses the anti-tumor activity resident T cells through ex vivo activation and expansion. This involves infusion single dose expanded TIL together with high IL-2 following preparative lymphodepleting chemotherapy. The United States Food Drug Administration approved lifileucel in 2024 as first autologous product for patients advanced cutaneous melanoma (CM), adding to list immunotherapies this highly immunogenic cancer. However, role TIL-ACT other solid tumors unclear, especially poorly cancers low mutational burden. In review, we describe historical development TIL-ACT, summarize clinical results CM, novel application metastatic uveal (UM), prototypic immunotherapy-resistant tumor. We will highlight key biologic differences between CM UM, their consequential influence on manufacturing UM-specific products, biomarkers precision UM.

Language: Английский

---

Low-exhaustion peripheral circulating γδ T cells serve as a biomarker for predicting the clinical benefit rate of non-small cell lung cancer (NSCLC) patients to chemotherapy or targeted therapy: a single-center retrospective study

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 30, 2025

Multiple studies have demonstrated that the abundance and functionality of γδ T cells are favorable prognostic indicators for prolonged survival in cancer patients. However, association between immunophenotype circulating therapeutic response NSCLC patients undergoing chemotherapy or targeted therapy remains unclear. Patients with EGFR wild-type (EGFR-WT) mutant (EGFR-Mut) non-small cell lung (NSCLC), diagnosed January 2020 2024, were included this study. Clinicopathological characteristics, treatment regimens, follow-up data retrospectively collected. Peripheral blood samples from 52 analyzed immunophenotypes αβ using full-spectrum flow cytometry. No significant differences observed proportions cells, nor expression immune exhaustion markers, epidermal growth factor receptor Notably, a high clinical benefit rate (responder, R) exhibited higher proportion Vδ2 compared to non-responders (NR), both EGFR-Mut (NR vs. R, P = 0.0437) EGFR-WT groups 0.0180). Additionally, marker PD-1 on was significantly lower responder group EGFR-Mut, 0.0050; EGFR-WT, Moreover, elevated levels TNF-α non-responders, irrespective mutation status 0.0055; 0.0007). These findings collectively suggest low critical contributors effectiveness therapies NSCLC. Targeting may represent promising strategy enhancing rates

Language: Английский

---

Tumor-Agnostic Therapies in Practice: Challenges, Innovations, and Future Perspectives

Cancers, Journal Year: 2025, Volume and Issue: 17(5), P. 801 - 801

Published: Feb. 26, 2025

This review comprehensively analyzes the current landscape of tumor-agnostic therapies in oncology. Tumor-agnostic are designed to target specific molecular alterations rather than primary site tumor, representing a shift cancer treatment. We discuss recent approvals by regulatory agencies such as FDA and EMA, highlighting that have demonstrated efficacy across multiple types sharing common alterations. delve into trial methodologies underpin these approvals, emphasizing innovative designs basket trials umbrella trials. These present unique advantages, including increased efficiency patient recruitment ability assess drug diverse populations rapidly. However, they also entail certain challenges, need for robust biomarkers complexities requirements. Moreover, we examine promising prospects developing rare cancers exhibit targets typically associated with more prevalent malignancies. By synthesizing insights, this underscores transformative potential It offers pathway personalized treatment transcends conventional histology-based classification.

Language: Английский

---

Safety and efficacy of combined treatment with tumor-infiltrating lymphocytes and oncolytic adenovirus TILT-123 in metastatic melanoma

Cell Reports Medicine, Journal Year: 2025, Volume and Issue: 6(3), P. 102016 - 102016

Published: March 1, 2025

Language: Английский

---

Advancing Breast Cancer Treatment: The Role of Immunotherapy and Cancer Vaccines in Overcoming Therapeutic Challenges

Vaccines, Journal Year: 2025, Volume and Issue: 13(4), P. 344 - 344

Published: March 24, 2025

Breast cancer (BC) remains a significant global health challenge due to its complex biology, which complicates both diagnosis and treatment. Immunotherapy vaccines have emerged as promising alternatives, harnessing the body’s immune system precisely target eliminate cells. However, several key factors influence selection effectiveness of these therapies, including BC subtype, tumor mutational burden (TMB), tumor-infiltrating lymphocytes (TILs), PD-L1 expression, HER2 resistance, microenvironment (TME). subtypes play critical role in shaping treatment responses. Triple-negative breast (TNBC) exhibits highest sensitivity immunotherapy, while HER2-positive hormone receptor-positive (HR+) often require combination strategies for optimal outcomes. High TMB enhances responses by generating neoantigens, making tumors more susceptible checkpoint inhibitors (ICIs); whereas, low may indicate resistance. Similarly, elevated TIL levels are associated with better immunotherapy efficacy, expression serves predictor inhibitor success. Meanwhile, resistance an immunosuppressive TME contribute evasion, highlighting need multi-faceted approaches. Current immunotherapies encompass range targeted treatments. HER2-directed such trastuzumab pertuzumab, block dimerization enhance antibody-dependent cellular cytotoxicity (ADCC), small-molecule inhibitors, like lapatinib tucatinib, suppress signaling curb growth. Antibody–drug conjugates (ADCs) improve targeting coupling monoclonal antibodies cytotoxic agents, minimizing off-target effects. ICIs, pembrolizumab, restore T-cell function, CAR-macrophage (CAR-M) therapy leverages macrophages reshape overcome While particularly TNBC, has demonstrated promise eliciting durable responses, efficacy varies across subtypes. Challenges immune-related adverse events, mechanisms, high costs, delayed remain barriers widespread vaccines—including protein-based, whole-cell, mRNA, dendritic cell, epitope-based vaccines—aim stimulate tumor-specific immunity. Though clinical success been limited, ongoing research is refining vaccine formulations, integrating identifying biomarkers improved patient stratification. Future advancements will depend on optimizing through biomarker-driven approaches, addressing heterogeneity, developing innovative therapies By leveraging strategies, researchers aim ultimately

Language: Английский

---

Behandlung des metastasierten Melanoms – Update 2025

DMW - Deutsche Medizinische Wochenschrift, Journal Year: 2025, Volume and Issue: 150(10), P. 562 - 569

Published: April 22, 2025

Immune checkpoint inhibition and targeted therapy with BRAF/MEK for BRAF-mutated melanoma have significantly improved progression-free overall survival in patients metastatic melanoma. Current research focuses on novel treatment strategies PD-1 resistance, neoadjuvant approaches, cellular therapies. 10-year follow-up data of randomized clinical trials show that both combined CTLA-4 immune alone can achieve long-term Potential surrogate markers response include a at 3 years after start reduction tumour burden least 80%. The management resistance remains challenge. Advances molecular pathology led to the identification new therapeutic targets. Several therapies are currently being evaluated as alternatives refractory or inhibition. In BRAF-mutant melanoma, is an alternative Real-world trial results sequencing suggest may improve first line setting, particularly absence prior adjuvant systemic therapy. Adjuvant leads while still pending. Neoadjuvant seems be promising conventional specific subgroups patients. Participation offers best opportunity benefit from latest options.

Language: Английский

---

Unveiling the Role of Anoikis Resistance in Lung Squamous Cell Carcinoma: A Prognostic Model and Immune Microenvironment Insights

Published: May 15, 2025

Purpose Advanced lung squamous cell carcinoma (LUSC) has poor prognosis due to local invasion, metastasis, therapeutic resistance, and a dynamic tumor microenvironment. While anoikis resistance contributes its malignancy, influence on the immune microenvironment (TIME) clinical outcomes in LUSC remains unclear. Methods Anoikis resistance-associated genes (ARGs) were identified using LASSO regression univariate Cox proportional hazards analysis. A prognostic signature was constructed validated both internal (TCGA-LUSC) external (GSE73403, GSE74777) cohorts. Functional characterization of performed single-cell transcriptomics pathway enrichment Comprehensive profiling conducted explore relationship between risk stratification TIME features. Core experimentally confirm their biological relevance. Results The ARG-based model stratified patients into high- low-risk subgroups with significant overall survival differences (log-rank p < 0.001). score an independent factor (HR: 3.91; 95% CI: 2.08–7.34). demonstrated robust predictive performance across datasets (AUC: >0.7). High-risk displayed immunosuppressive characteristics, including reduced CD8 + T infiltration (p = 0.004), increased stromal content 0.01), lower predicted immunotherapy responsiveness 0.007). Three key ARGs—SDCBP, RPS6KA1, ITGA3—were as critical regulators functional assays confirming SDCBP's oncogenic role promoting malignancy. Conclusion This effectively predicts revealed strong associations landscape alterations, response, offering framework for precision management.

Language: Английский

---

Cancer Vaccines: Recent Insights and Future Directions

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(20), P. 11256 - 11256

Published: Oct. 19, 2024

The field of cancer immunotherapy has seen incredible advancements in the past decades. mRNA-based vaccines generating de novo T cell responses, particularly against tumor-specific antigens (TSAs), have demonstrated promising clinical outcomes and overcome diverse challenges. Despite high potential neoantigens to provide personalized immunotherapies through their tumor specificity immunogenicity, challenges related scarcity immunogenic neoepitopes prompted continuous research towards finding new tumor-associated (TAAs) broader therapeutic frameworks, which may now learn from genuine successes obtained with neoantigens. As an example, human endogenous retroviruses (HERVs) emerged as alternatives due tumoral expression ability elicit both reactivity B responses associated efficacy existing immunotherapies. This review aims assess status limitations TSA-directed mRNA lessons that can be derived these checkpoint inhibitor studies guide TAA vaccine development. We expect shared cell, CD4 CD8 antigen presentation will key stimulate expansion for tumors do not contain pre-existing tertiary lymphoid structures. When structures are present highly mutated tumors, current checkpoint-based show even immune privileged sites, hold broaden more types stages.

Language: Английский

---